Clinical trials finally public!

The World Health Organization announced that it was creating an internet portal on which would be available all the clinical trials taking place around the world.

The interest of such a centralization (which had already been undertaken by some pharmaceutical laboratories)is that of avoiding duplications and unnecessary repetitions. It would also provide scientists with the possibility of checking for negative results (which are seldom published).

On the plane of bioethics, it is certain that this tool also has its importance as it would allow specialized associations and interested individuals to check out for clinical trials being conducted on human patients. The lack of transparency on clinical trials has often been incriminated, especially when these trials are conducted in third world countries.

However, that transparency seems to be quite far away for the time being. One can recall clinical trials being conducted on AIDS in some African countries without real information being given to the patients. On the other hand, clinical trials being conducted on patients in end of life have also to undergo scrutiny (cfr. for instance one of the clinical trials available on the WHO site which talks about tests on cancer patients of which the benefits are clearly not evident compared to the secondary effects:

Palliation of thoracic symptoms measured over 52 weeks after randomization. The data collection schedule for follow-up is presented in table 2. A maximum of 33 questionnaires per patient would be sent in case follow-up could be completed. The first questionnaire was given before randomization, the last questionnaire in the 52nd week after randomization. Data about effectiveness of the treatment and QOL were based on the Rotterdam Symptom Checklist (10). Seven symptoms could be scored each on a four point validated scale from 1 (no complaints) to 4 (severe complaints) (10). The baseline total symptom score had to be 8 indicating that the patient had at least one tumor related complaint. The maximum total symptom score could be 28 indicating the patient had all seven complaints in the worst degree. After response the lowest total symptom score could be 7, having no complaints at all. Palliation was defined as a average total score below the baseline score.
Secondary Outcome(s)
1. Toxicity, Quality of Life (QOL), and survival. 2. Quality of life was measured using the EuroQol classification system (EQ-5D), consisting of five questions on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression 3. In addition, information about acute toxicity as nausea, vomiting, and radiation esophagitis induced dysphagia was collected, based on the NCIC CTG Expanded Common Toxicity Criteria 4. Patients were also asked to provide information about costs. Together with quality of life data, these data will be published separately in a cost-utility analysis. 5. Follow up after 52 weeks was continued by the data manager, who made 3-monthly inquiries after survival of the patient.

Evidently, rules of bioethics request that the physician compares the potential benefits to the inconvenience resulting from the trial for the patient. However, who can really say that the patients have made a sufficiently informed consent to this trial, especially when being at the end of their life?

Hence, the main interest of publishing online all clinical trials being held, is mainly to favour a control by the citizen or pressure groups on these trials.

Pro-euthanasia militants try to sway French presidential candidates

It was to be expected, though the unsavory political opportunism of the pro-euthanasia has something of sickening.

As both contendants to the presidential elections are disputing a harsh campaign in a race too close to call, the ADMD (Association pour le Droit de Mourir dans la Dignité) launched a “white book” titled “End of life, a new law is indispensable”.

See the article below of Cécile Prieur, though her account is thoroughly partisan.

Les militants pro-euthanasie interpellent les candidats

LE MONDE | 29.01.07

In that respect, whereas opinions are rather confused at the UMP, Union pour une Majorité Populaire of Nicolas Sarkozy, the Socialist party is known for supporting unreservedly the idea of legalizing euthanasia. The proposition appears clearly in its program and the Socialist candidate, Ségolène Royal said in August 2006 that she was “in full agreement with the project of [her] party” on euthanasia.

If old people do not wish to be euthanized in France, at least now they know for whom not to vote…

Le PS se prononce en faveur d'une "aide active" à mourir
LE MONDE | 29.01.07

The debate on euthanasia reappears in Italy

The death of a patient suffering of muscular dystrophia in the days before Christmas reintroduced spectacularly the debate on euthanasia in Italy.

Piergiorgio Welby, 60, the patient had introduced an action in justice against the Italian government claiming “the right to die”. However, the Italian courts had claimed a legal void and referred the case to political authorities.

In Italy, of course, euthanasia is a crime, punished of six to fifteen years imprisonment. However, as elsewhere in Europe, pro-euthanasia militants are lobbying aggressively to obtain the legalization of euthanasia. Hence, unsurprisingly, the death of Welby became a political opportunity for the Radical Party of Emma Bonino, a party known for its commitment to all the most extreme causes, such as homosexual marriage, euthanasia, drugs legalization.

On the 20^th of December, the doctor of Welby took away the respirator which allowed Welby to live after giving him painkillers. Members of the Radical party were present at what was presented to the medias as an emotional farewell of Welby to his family – he died on a music of Bob Dylan was one of the involuntarily comical details released.

Strictly speaking, this is not a case of euthanasia, since there was no delivery of a lethal product. Taking advantage of the unclear situation in ethics and law in Italy, the physicians of Welby maintained that they had acted on the basis of the “right to refuse care” which is recognized by the Italian constitution.

However, the situation of Welby was not such, medically, that he was in imminent danger of death, had the respiratory assistance been maintained. Hence, the act posed by the physician of Welby was effectively a homicide, independently of the request of Welby.

The moral position was so clear, that the Catholic church decided to deny Welby religious funerals because the death had been “provoked”, hence causing the furor of several “progressive” Catholics.

Nevertheless, the debate on euthanasia has left traces either within the right or within the left. Whereas Silvio Berlusconi, the mediatic leader of Forza Italia opportunistically pronounced himself in favour or the “liberty of choice” of everyone in the matter, the composite nature of the left majority of Romano Prodi places the latter before a dilemma: while some as the ultra-active Radicals are favourable to a legalization of euthanasia, this would be a casus belli for some more moderate center-left members of the majority such as the left-wing Christian-democrats.

Stem cells : the Vatican defends research on multipotent cells against totipotent cells

On Saturday 16 September, there was an International Congress of Stem cells in Vatican on stem cell research. The Congress was organized by the Pontifical Academy for Life, the International Federation of Catholic Medical Associations and the Foundation Jerôme Lejeune.

Stem cell research has been generally centered on totipotent cells (initial embryonic cells which may develop into any type of cells), developed from embryos. This type of research is opposed by the Vatican for which the destruction of the embryo (which is required to obtain the cells) is in opposition with the Catholic doctrine of the sanctity of life.

In fact, another track is also followed by researchers: the possibility of using multipotent cells (cells with a limited power of differentiation) to develop cures. The discovery of these type of stem cells notably in the umbilical cord, has been highlighted recently by the news of famed soccer players having congealed the stem cells of their children’s umbilical cord in prevision of possible care for future wounds.

However acceptable the solution might appear for the Catholic church – to which it offers the possibility of appearing as being in phase with progress – the participants to the Congress also insisted that the research on stem cells left many questions open.

Some of the questions left open is notably whether replacing ill cells by healthy one would not lead to an extension of the disease to the grafted cells (the question being especially interesting for degenerative diseases such as the Alzheimer illness).

Other questions considered were the question of scientific fraud (consider notably the Korean fraud upon which we wrote previously in February), and notably arguments by proponents of research on embryonic stem cells that these cells could be taken without damaging the embryo…

The Vatican is trying in fact to orient research on stem cells in a sense more acceptable to Catholic convictions, especially since the potential appeal of treatment by stem cells seems to have convinced public opinion.

Prevention of tuberculosis and discrimination : an opinion of the French national consultative committee for bioethics

A recent question that arose with the regression of tuberculosis as a pathology and at the same time its apparition under more virulent forms in a pauperized population brought up the question of the use of continuing preventive vaccination of the whole infantile population with BCG.

The French committee for bioethics, the Comité Consultatif National d’Ethique pour les sciences de la vie et de la santé (CCNE) thus requested to give an opinion by the General Director for Public Health in France.

The question was formulated in these terms :

Suppression of the obligatory nature of the vaccination of children by BCG in order to reserve this vaccination to the risk populations exclusively

Systematic detection of tuberculosis through intradermic reaction to tuberculine, targeted on some children at school.

Systematic detection of tuberculosis by radiography and intradermic reaction to tuberculine when any person is hired who has to work with those children concerned by the tracking and the vaccination.

Specifically, we are talking here of children mainly from immigrant populations, in areas with endemic tuberculosis.

The CCNE answered by considering five points : the epidemiology of tuberculosis, detection of tuberculosis, vaccination, public health and ethical questions.

Epidemiology :

The CCNE recalls the available medical data, i.e. that there is an incidence of 10 new cases of tuberculosis per 100.000 inhabitants per year, since 1997. Actually there is a disparity in the presence of tuberculosis according to the nationality : about 5.7 cases per 100.000 inhabitants for French nationals, and much higher figures for foreign nationals : 74.2 cases per 100.000 inhabitants, this figure rising to 114.3 per 100.000 inhabitants in the region of Paris.

The CCNE thus found that there is a serious risk of contamination for fragilized populations.

Detection :

A systematic detection of tuberculosis is slowly disappearing. Mostly there are radiographies taken when hiring for some forms of employment or at the entrance in prison. Detecting persons affected by tuberculosis is all the more difficult since the tuberculine test reacts just as well to BCG as to tuberculosis. While fragilized populations would be the most in need of such detection, they are also those who have the least access to these procedures. Reserving detection to these populations might also end up by causing ethical problems as the CCNE examines further in its opinion.

Vaccination :

The coverage rate by BCG vaccination is of about 95 % at the age of six years, which is considered as excellent. With the change in furnisher of the BCG, the technique of vaccination also changed. Whereas before it was applied by a « multipuncture » ring, now it will have to be injected through intradermic injection. The problem being that many doctors do not have the necessary skills for practicing such injections (incidentally, that says a lot of the GP’s in France!). Secondary effects might be suppurations, and the presence of a scar. The CCNE finds that while the secondary effects and the low practicability of the new vaccination form are elements to be considered in favour of abandoning systematic vaccination, without a generalised detection of tuberculosis it may be discriminating without being efficient.

Public health:

The CCNE here starts examining the foundations of prevention, and notably recalls that protecting a group necessarily means limiting the freedom of the individual. However, to approach this problem, the CCNE recalls again that it had emitted the idea of a “debt of the society” towards the person having to be treated, in order that this person may gain more rights towards the society through its illness, than the society has on her.

Ethical questions:

This is the most interesting part, since this blog is concerned with bioethical questions. The CCNE signals before anything that the use of the verb “to target” is not innocent.

With a targeted vaccination, the CCNE signals that it might be considered as discriminating against, even if it is explained as being a “positive discrimination”. And the risk is very present of having to use force and policing to enforce this vaccination. In addition, one day, this “targeted” vaccination may become “segregative” in the terms of the CCNE.

More fundamentally, the ethics committee recalls that the problem of tuberculosis is also that of accessing the health structures without fear. Fear might bring up strategies of avoidment which might be counter-productive for the public health objective.

Recommandations:

The CCNE makes several recommandations (it only has a consultative nature, it cannot take decisions). Considering previous epidemiological studies, notably in Sweden where BCG was stopped several years ago (although the CCNE does not refer explicitly to these), the CCNE warns against a possible interruption of the BCG vaccination.

Any change in the vaccination policies should be accompanied by an increase in the generalised detection effort, especially with people coming from zones where tuberculosis is endemic...

At the same time, any specific attention to exposed populations should ensure that the detection and vaccination efforts be not transformed into a general policy against such or such population; exclusively basing these efforts on socio-economic considerations might be a way to exercise a disguised adverse discrimination.

The CCNE concludes by recommending an increased effort in the training of school physicians, GP’s etc, in order to sensibilise them to the aid to vulnerable persons.

You may download the whole opinion (in French) here.